Absence of a clinical correlation for complement-mediated, infection-enhancing antibodies in plasma or sera from HIV-1-infected individuals. Multicenter AIDS Cohort Study Group.

Neutralizing and complement-mediated infection-enhancing antibodies to HIV-1 were measured in sera or plasma from 54 HIV-1-positive individuals at various stages of disease, and from an additional 36 HIV-1-positive individuals for whom no clinical data were available. Antibodies were measured in microtiter infection assays utilizing MT-2 cells and the IIIB strain of HIV-1. The frequency of detection of both types of antibodies was identical, being 77 out of 90 cases (86%). Neutralizing and infection-enhancing antibodies were not always found together, and in four cases both were undetectable. No correlation was found between titers of either type of antibody and stage of disease. Furthermore, titers of infection-enhancing antibodies at early stages of disease did not predict rate of disease progression.

Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site.

OBJECTIVE: To assess the extent of nosocomial transmission and risk factors associated with tuberculin skin test (TST) conversions among healthcare workers (HCWs) exposed to a patient with genitourinary Mycobacterium tuberculosis. DESIGN: Retrospective cohort study of exposed HCWs. SETTING: A 275-bed community hospital in Middle Tennessee. PARTICIPANTS: A total of 128 exposed HCWs and the index patient, who required drainage of a prostatic abscess and bilateral orchiectomy and expired after a 27-day hospitalization. Disseminated tuberculosis was diagnosed at autopsy. METHODS: Contact tracing was performed on exposed HCWs. Logistic regression was used to identify independent risk factors associated with TST conversion. RESULTS: A total of 128 HCWs were exposed to the index patient. There was no evidence of active pulmonary tuberculosis throughout the patient's hospitalization; TST conversions occurred only among HCWs who were exposed to the patient during or after his surgical procedures. A total of 12 (13%) of 95 exposed HCWs who were previously nonreactive had newly positive TST: 6 of 28 nurses, 3 of 3 autopsy personnel, 2 of 17 respiratory therapists, and 1 of 12 surgical staff. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TST conversion among nurses (odds ratio, 9; 95% confidence interval, 1.2-67; P=.03). CONCLUSION: Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis.

Falsely elevated serum creatinine levels secondary to the presence of 5-fluorocytosine.

The Kodak Ektachem (Eastman Kodak Co., Rochester, NY) is a new clinical chemistry analyzer that uses an enzymatic method to measure creatinine. The authors report the case of a patient with falsely elevated creatinine levels that were caused by the presence of 5-fluorocytosine. A review of the literature confirmed that this can occur, but well documented reports are not found. In order to determine the magnitude of this interference, the authors plotted creatinine levels versus 5-FC concentration. Significant interference is seen with therapeutic levels of 5-FC. Both clinicians and pathologists should be aware of this phenomenon.

Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.

The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study. Patients were randomized to receive 2.5 mg dronabinol twice daily or placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol was associated with increased appetite above baseline (38% vs 8% for placebo, P = 0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs 7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were mostly mild to moderate in severity (euphoria, dizziness, thinking abnormalities); there was no difference in discontinued therapy between dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS.

Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.

We studied the effects of long-term (12 months) dronabinol in 94 late-stage acquired immunodeficiency syndrome (AIDS) patients (mean CD4 count of 45/mm3) who previously participated in a 6-week study (placebo versus dronabinol). All patients received dronabinol orally-2.5 mg twice daily (90%) or 2.5 mg once daily (10%). Appetite was measured using a visual analogue scale for hunger (VASH). Dronabinol was associated with consistent improvement in mean appetite. Patients previously treated with dronabinol continued to show improvement in VASH (percent change from baseline of 6-week trial: 48.6-76.1% at each month), whereas those previously treated with placebo exhibited substantial improvement in mean appetite, particularly during the initial 4 months of treatment (48.5-69.9%). Thereafter, dronabinol was associated with a VASH change at least twice baseline. Patients tended toward stable body weight for at least 7 months. Adverse events were primarily related to known central nervous system effects of dronabinol. These data support long-term, safe use of dronabinol for anorexia associated with weight loss in patients with AIDS.

Septic shock and acute respiratory distress syndrome after salpingitis caused by Streptococcus pyogenes group A.

A 32-year-old woman with acute salpingitis had signs and symptoms of sepsis, with hypotension, renal failure, acute respiratory distress syndrome, and disseminated intravascular coagulation. Streptococcus pyogenes group A was grown from blood cultures taken at the onset of illness, and salpingitis was confirmed at laparotomy. The patient recovered after appropriate antimicrobial and intensive supportive therapy.

Expression of group IA phospholipase A2 in Pichia pastoris: identification of a phosphatidylcholine activator site using site-directed mutagenesis.

Site-directed mutants of the group IA phospholipase A(2) from cobra venom were constructed and expressed in the methylotrophic yeast Pichia pastoris to probe for the proposed phosphatidylcholine (PC) activator site. Previous crystallographic and molecular modeling studies have identified two regions of the enzyme as likely candidates for this site. Residues Glu-55, Trp-61, Tyr-63, Phe-64, and Lys-65 were mutated to test the site advanced by Ortiz et al. [(1992) Biochemistry 31, 2887-2896] while Asp-23 and Arg-30 were mutated to assess the site proposed by Segelke et al. [(1998) J. Mol. Biol. 279, 223-232]. Expressed enzymes were purified by affinity chromatography and analyzed by SDS-PAGE, Western blotting, electrospray ionization mass spectroscopy, and circular dichroism. Both phospholipid headgroup specificity and rates of hydrolysis on monomeric PC substrates were determined and found to be similar for native, wild-type, and all of the mutant enzymes. These results suggest that all of the expressed enzymes were properly folded and contained functional catalytic sites. Mutations of the aromatic residues in the Ortiz site generally had little effect on PC activation, arguing against the importance of this region of the enzyme for PC activation; however, these aromatic amino acids appeared to be important for interfacial activation. In contrast, the D23N mutant in the Segelke site reduced PC activation by 10-fold without affecting activity toward micellar phosphatidylethanolamine substrates. Similar results were found with the D23N/R30M double mutant, suggesting that this region is critical for PC activation. These results provide evidence for the Segelke site as a PC activator site that is distinct from the catalytic site.

Increased incidence of syphilis in Tennessee during the 1980s: challenges for a new decade.

Although recent increases in the incidence of syphilis are well known to public health officials, the general medical community is less well informed regarding the dramatic rise in cases. We present trend data from Nashville and Tennessee over the past decade. These statistics emphasize specific factors, such as drug abuse, that contribute to new difficulties in controlling this sexually transmitted disease.

Gestational exposure to rubella vaccinees: a population surveillance study.

Over a two-year period an attempt was made to identify instances of transmission of rubella vaccine virus from rubella vaccinees to pregnant women in Nashville-Davidson County, Tennessee. Approximately 24,000 children were immunized in a mass campaign at the outset of the study. Several prospective surveillance methods of 11,635 women and their new babies were employed. Attempts were made to recover rubella virus from throat swabs of 10,951 newborns. No rubella vaccine virus was recovered. Wild rubella virus was isolated from a single infant with the congenital rubella syndrome whose mother had natural rubella during the first month of pregnancy. Rubella virus was not isolated from the products of 240 abortions. There were no seroconversions among 3990 women who had paired sera available for study. Clinical and serologic follow-ups of infants judged to be a high risk because of intimate maternal exposure to vaccine virus revealed no late manifestations of congenital rubella infection. A history of close maternal contact with vaccinees during the three months before and the three months following conception was not associated with an increased incidence of congenital anomalies or clinical features seen with congenital rubella infection. Thus, no evidence of vaccine virus transmission was found, providing further evidence of the safety of rubella vaccine under field conditions. A seroepidemiologic study of 8824 pregnant women revealed the expected decline in rubella susceptibility with increasing age. When age was controlled, the variables of race, parity, and educational achievement produced no major influence on immunity.

Paecilomyces cellulitis in a renal transplant patient: successful treatment with intravenous miconazole.

We report an immunosuppressed host with an unusual fungal infection which resolved during intravenous therapy with a new antifungal agent. This agent, miconazole, appears to have minimal side effects and a broad antifungal spectrum, and it deserves consideration for treatment of susceptible organisms.

The reporting of communicable diseases: a controlled study of Neisseria meningitidis and Haemophilus influenzae infections.

Surveillance systems for communicable diseases in the United States are primarily passive. We compared the passive reporting system for invasive disease caused by Neisseria meningitidis and Haemophilus influenzae with a concurrent, active laboratory-based system in the four metropolitan counties of Tennessee. The passive reporting system identified approximately 50% of all cases that were identified by the active system and accurately reflected trends in disease occurrence during the study period. Of all reported cases, physicians contributed fewer than 4%. Nearly 40% of all hospitals in the study area did not participate in the passive system. This lack of participation resulted in disproportionately increased reporting of disease among blacks. Inconsistencies in case definition within the state also contributed substantially to underreporting and lack of demographic representativeness of reported cases. The median reporting interval (the time from the onset of disease to transmission of the case report to the Centers for Disease Control and Prevention) was 24 days (range, 5-157 days). Efforts to improve surveillance of those infections for which isolation of a pathogen is tantamount to a diagnosis should concentrate on laboratory-based reporting and the use of currently available computer telecommunication systems.

Recurrences and sequelae of rheumatic fever in Nashville. A follow-up study.

A follow-up study of 311 patients who acquired rheumatic fever in Nashville, Tenn, during the period from 1963 to 1969 showed that 53% took penicillin prophylaxis regularly, 36% did not take it as recommended, and 11% did not take it at all. There were no recurrences among those who received prophylaxis by injection regularly, six recurrences among those who took oral prophylaxis regularly, and no recurrences among 45 subjects who did not take prophylaxis. Among these 45, however, were 29 for whom prophylaxis was not recommended by their physicians. The original study indicated that the incidence of acute rheumatic fever among blacks was twice as high as among whites. In the present study, incidence of rheumatic heart disease and recurrences was substantially higher among blacks than among whites.

A survey of 251 patients with acute syphilis treated in the collaborative penicillin study of 1943-1950.

The dramatic and apparently curative effect of penicillin for the treatment of acute syphilis led to follow-up studies for only comparatively brief periods, and the acceptance of the long-term benefit of penicillin has rested on uncontrolled clinical impressions. More certainty about the efficacy of penicillin was sought by a follow-up review of 251 patients treated between March 1944 and December 1950 under the Penicillin Study of the Office of Scientific Research and Development (OSRD) and continued under U. S. Public Health Service after World War II. Eighty-eight patients were interviewed and examined. Telephone conversation or correspondence was had with 43 subjects; an additional nine are known to be living but did not respond to letters. Thirty-two patients died greater than or equal to 20 years after treatment, and 21 patients died within less than 20 years of treatment. Fifty-eight patients could not be found. Treatment failures were documented. Syphilis was not shown to be the cause of disability or death, except for a patient with meningovascular syphilis who died soon after initial treatment. Disabilities recorded and deaths documented revealed only diseases common to any middle-aged population. The outcomes of 17 pregnancies of women treated for acute syphilis were documented. Blood samples obtained from the 88 subjects examined were tested at the Center for Disease Control (Atlanta, Ga.); the results are recorded and discussed. Methods for locating the patients are described, and the psychosocial findings for the 88 patients interviewed are presented. The study has confirmed the clinical impressions of the therapeutic effectiveness of penicillin, which have been accepted for greater than 30 years.

Risk factors for invasive pneumococcal disease in children: a population-based case-control study in North America.

OBJECTIVE: To identify risk factors for invasive pneumococcal disease, including penicillin-resistant infections, among children 2 to 59 months of age. DESIGN: Case-control study. PARTICIPANTS: Patients with invasive pneumococcal infections identified by population-based surveillance (n = 187) and controls identified through random-digit telephone dialing (n = 280). OUTCOME MEASURES: Invasive pneumococcal disease was defined as isolation of Streptococcus pneumoniae from a normally sterile site. Patients 2 to 59 months of age who were residents of one of four active surveillance areas were included. S pneumoniae isolates were tested by broth microdilution. Isolates with a minimum inhibitory concentration to penicillin >/=2 microg/mL were considered resistant. RESULTS: Invasive pneumococcal disease was strongly associated with underlying disease and with day care attendance in the previous 3 months. Among 2- to 11-month-olds, current breastfeeding was associated with a decreased likelihood of invasive pneumococcal disease (odds ratio, 0.27; 95% confidence interval: 0.08, 0.90). Penicillin-resistant infections were independently associated with day care attendance, at least one course of antibiotics, and at least one ear infection in the previous 3 months. CONCLUSIONS: This study shows the association of underlying illnesses, day care attendance, and lack of breastfeeding with risk of invasive pneumococcal disease in children. The association of recent antibiotic use and infection with penicillin-resistant S pneumoniae highlights the need to avoid unnecessary antibiotic use in children.

Homotypic antibody responses to fresh clinical isolates of human immunodeficiency virus.

Human immunodeficiency virus type 1 (HIV-1) exhibits extensive genomic and antigenic diversity, which is thought to contribute to the failure of the host's immune response to control infection and prevent clinical progression. Part of this failure may be due to utilization by the virus of antigenic variation as a means to escape protective immune responses. Antibody-escape variants of HIV-1 were studied here using fresh clinical isolates and autologous plasmas. HIV-1 was isolated from the plasma of seven people who were all seropositive for at least 2 years, and symptomatic sometime during that period. Isolated viruses were confirmed as HIV-1 by the presence of reverse transcriptase activity in infected culture supernatants, and by positive immunofluorescence using human monoclonal antibody to HIV-1 core protein. Plasma from these people were positive by Western immunoblot (DuPont) for most major HIV-1 (strain IIIB) antigens. These plasmas neutralized three laboratory strains of HIV-1 (i.e., IIIB, RF, and MN) but did not neutralize the homotypic strain in five cases, and had greatly reduced neutralizing titers against the homotypic strain in two cases. Homotypic neutralizing antibodies were absent in autologous plasma obtained 3 months later. When antibody titers were measured by fixed-cell indirect immunofluorescence assays (IFAs), high titers of IgG (1:6400 to 1:25,600) were detected against HIV-1 IIIB, while low titers of only 1:20 to 1:160 were detected against homotypic viral antigens at the time of virus isolation, and remained low 12 and 16 weeks later. No class IgA, IgD, IgE, or IgM antibodies to homotypic viral antigens, as possible IgG-blocking antibodies, were detected by fixed-cell IFAs. Cross-reactions with heterologous donor's plasmas were observed in some cases, and in these cases the cross-reactions were unidirectional. Live-cell IFAs detected IgG in patient's plasma to HIV-1 IIIB-infected cells but not to cells infected with homotypic isolates. These results suggest that it is common for neutralization-resistant HIV-1 variants to appear during the course of infection, and that all or most antigens of these variants are capable of escaping antibody recognition.

Group V phospholipase A(2)-dependent induction of cyclooxygenase-2 in macrophages.

When exposed for prolonged periods of time (up to 20 h) to bacterial lipopolysaccharide (LPS) murine P388D(1) macrophages exhibit a delayed prostaglandin biosynthetic response that is entirely mediated by cyclooxygenase-2 (COX-2). Both the constitutive Group IV cytosolic phospholipase A(2) (cPLA(2)) and the inducible Group V secretory phospholipase A(2) (sPLA(2)) are involved in the cyclooxygenase-2-dependent generation of prostaglandins in response to LPS. Using the selective sPLA(2) inhibitor 3-(3-acetamide-1-benzyl-2-ethylindolyl-5-oxy)propane sulfonic acid (LY311727) and an antisense oligonucleotide specific for Group V sPLA(2), we found that induction of COX-2 expression is strikingly dependent on Group V sPLA(2), which was further confirmed by experiments in which exogenous Group V sPLA(2) was added to the cells. Exogenous Group V sPLA(2) was able to induce significant arachidonate mobilization on its own and to induce expression of the COX-2. None of these effects was observed if inactive Group V sPLA(2) was utilized, implying that enzyme activity is crucial for these effects to take place. Therefore, not only delayed prostaglandin production but also COX-2 gene induction are dependent on a catalytically active Group V sPLA(2). COX-2 expression was also found to be blunted by the Group IV cPLA(2) inhibitor methyl arachidonyl fluorophosphonate, which we have previously found to block Group V sPLA(2) induction as well. Collectively, the results support a model whereby Group IV cPLA(2) activation regulates the expression of Group V sPLA(2), which in turn is responsible for delayed prostaglandin production by regulating COX-2 expression.

Active surveillance for toxic shock syndrome in the United States, 1986.

Active surveillance for toxic shock syndrome (TSS) was established in 1986 in Los Angeles County and in the states of Missouri, New Jersey, Oklahoma, Tennessee, and Washington. Case reports were solicited through biweekly contact with all acute-care hospitals. One hundred sixteen definite and 63 probable cases were reported; 85% of the cases occurred in female patients and 15% in male patients. Among cases in females, 83 (55%) were menstrual; the mean age of the patients with menstrual cases was 23 years (range, 12-46 years). The overall incidence of TSS was 0.53/100,000. The cumulative incidence varied significantly by region, ranging from 1.23/100,000 in Oklahoma to 0.22/100,000 in New Jersey (P = .0001); the incidence in all other areas ranged from 0.39/100,000 to 0.70/100,000. The incidence of menstrual TSS was 1.05/100,000 women 15-44 years of age and peaked in women between the ages of 15 and 19 years at 1.52/100,000. The incidence was higher in whites than in nonwhites for both menstrual TSS (1.21/100,000 vs. 0.34/100,000, P = .002) and nonmenstrual TSS (0.30/100,000 vs. 0.14/100,000, P = .031). Our data indicate that TSS continues to be a cause of morbidity. Although there is underreporting in national passive surveillance, the proportion of menstrual cases reported through active surveillance was similar to that reported to the passive system in 1986.

Bacterial meningitis in the United States in 1995. Active Surveillance Team.

BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.